title: Involvement of 5-HT3 receptors in pudendal inhibition of bladder overactivity in cats.
abstract: In the present study, the role of 5-HT3 receptors in pudendal neuromodulation of bladder activity and its interaction with opioid receptors were investigated in anesthetized cats. The bladder was distended with either saline to induce normal bladder activity or with 0.25% acetic acid (AA) to induce bladder overactivity. Pudendal afferent nerves were activated by 5-Hz stimulation at multiples of the threshold (T) intensity for the induction of anal twitching. AA irritation significantly reduced bladder capacity to 16.5 ± 3.3% of saline control capacity, whereas pudendal nerve stimulation (PNS) at 1.5-2 and 3-4 T restored the capacity to 82.0 ± 12% (P = 0.0001) and 98.6 ± 15% (P < 0.0001), respectively. Cumulative doses (1-3 mg/kg iv) of ondansetron, a 5-HT3 receptor antagonist, eliminated low-intensity (1.5-2 T) PNS inhibition and reduced high-intensity (3-4 T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5-2 and 3-4 T significantly increased bladder capacity to 173.2 ± 26.4% (P = 0.036) and 193.2 ± 22.5% (P = 0.008), respectively, of saline control capacity, but ondansetron (0.003-3 mg/kg iv) did not alter PNS inhibition. Ondansetron (0.1-3 mg/kg) also significantly (P < 0.05) increased control bladder capacity (50-200%) during either AA irritation or saline distention. In both conditions, the effects of low- and high-intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg iv) significantly (P < 0.05) decreased control bladder capacity (40-70%) during either AA irritation or saline distention but failed to affect PNS inhibition. This study revealed that activation of 5-HT3 receptors has a role in PNS inhibition of bladder overactivity. It also indicated that 5-HT3 receptor antagonists might be useful for the treatment of overactive bladder symptoms.
authors.affiliation: Dept. of Urology, Univ. of Pittsburgh, 700 Kaufmann Bldg., Pittsburgh, PA 15213, USA.
authors.forename: Zeyad
authors.initials: Z
authors.lastname: Schwen
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuta
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D060525:Pudendal Nerve / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D009270:Naloxone; D017294:Ondansetron
keywords: 5-HT3 receptor; neuromodulation; opioid receptor; overactive bladder; pudendal; serotonin